Study of I Line FOLFOX + Panitumumab vs 5FU + Panitumumab in RAS and BRAF WT Metastatic Colorectal Cancer Elderly Patients (PANDA)
Elderly Metastatic Colorectal Cancer Patients
About this trial
This is an interventional treatment trial for Elderly Metastatic Colorectal Cancer Patients
Eligibility Criteria
Inclusion criteria
- Written informed consent to study procedures and to molecular analyses.
- Histologically proven diagnosis of colorectal cancer.
- Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease.
- At least one measurable lesion according to RECIST1.1 criteria.
- Availability of a tumoral sample (primary and/or metastatic sites).
- Age ≥ 70 years.
- ECOG PS 1 or 2 for patients aged 70 to 75 years; ECOG PS 0 or 1 for patients aged > 75 years.
- Life expectancy of at least 12 weeks.
- Previous adjuvant chemotherapy allowed only if with fluoropyrimidine monotherapy and more than 6 months elapsed between the end of adjuvant and first relapse.
- RAS and BRAF status wild-type of primary colorectal cancer or related metastasis, centrally assessed.
- Neutrophils ≥1.5 x 109/L, Platelets ≥100 x 109/L, Hgb ≥ 9 g/dl.
- Total bilirubin ≤ 1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases) alkaline phosphatase ≤ 2.5 x UNL (or <5 x UNL in case of liver metastases).
- Creatinine clearance ≥ 50 mL/min or serum creatinine ≤1.5 x UNL.
- Male subjects with female partners of childbearing potential must be willing to use adequate contraception as approved by the investigator (barrier contraceptive measure or oral contraception).
- Geriatric assessment by means of G8 screening tool and CRASH score.
- Will and ability to comply with the protocol.
Exclusion criteria
- Previous treatment for metastatic disease.
- Radiotherapy to any site within 4 weeks before the study.
- Previous adjuvant oxaliplatin-containing chemotherapy.
- Previous treatment with EGFR inhibitors.
- Untreated brain metastases or spinal cord compression or primary brain tumors.
- History or evidence upon physical examination of CNS disease unless adequately treated.
- Symptomatic peripheral neuropathy > 1 grade NCIC-CTG criteria.
- Creatinine clearance < 50 mL/min or serum creatinine >1.5 x UNL.
- Clinical signs of malnutrition.
- Neutrophils <1.5 x 109/L, Platelets <100 x 109/L, Hgb <9 g/dl.
- Diagnosis of interstitial pneumonitis or pulmonary fibrosis.
- Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration.
- Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (≤6 months), myocardial infarction (≤6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication.
- Treatment with any investigational drug within 30 days prior to enrollment or 2 investigational agent half-lives (whichever is longer)
- Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ.
- Lack of physical integrity of the upper gastrointestinal tract, malabsorption syndrome, or inability to take oral medication.
- Definite contraindications for the use of corticosteroids and antihistamines as premedication.
- Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs.
- Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies.
- Sexually active males unwilling to practice contraception (barrier contraceptive measure or oral contraception) during the study and until 6 months after the last trial treatment.
Sites / Locations
- Istituto Oncologico Veneto IRCCS
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
FOLFOX plus panitumumab
5FU/LV plus panitumumab
Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; Oxaliplatin 85 mg/sqm iv over 2 hours, day 1; L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.
Panitumumab 6 mg/kg iv over 60 minutes, day 1; if the first infusion is tolerated, then subsequent infusions may be administered over 30 to 60 minutes; L-Leucovorin 200 mg/sqm iv over 2 hours, day 1; 5-fluoruracil 2400 mg/sqm 48 h-continuous infusion, starting on day 1; to be repeated every 2 weeks for a maximum of 12 cycles. If no progression occurs, patients will receive maintenance panitumumab at the same dose used at the last cycle of the induction treatment. Panitumumab will be repeated biweekly until disease progression, unacceptable toxicity or patient's refusal.